Cilostazol prevents the degradation of collagen type II in human chondrocytes.

The alteration of extracellular matrix (ECM) in cartilage during the pathological development of Osteoarthritis (OA) changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. Healthy cartilage matrix mainly contains collagen type II, which is degraded by matrix metalloproteinase13 (MMP13), an important molecules responsible for joint damage in OA. Cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2-(1H)-quinolinone) is a medication approved by the US Food and Drug Administration and used in the alleviation of the symptom of intermittent claudication in individuals with peripheral vascular disease. In this study, we reported that cilostazol is able to suppress the degradation of type II collagen in human chondrocytes induced by IL-1β. Mechanistically, cilostazol treatment leads to inhibiting the expression of IRF-1, thereby prevents the induction of MMP-13. Signal transducers and activator of transcription 1 (STAT1) has been reported to play an essential role in regulating the activation of IRF-1. Our results indicated that cilostazol suppresses the activation of STAT1 by mitigating the phosphorylation of STAT1 at Ser727 and tyrosine phosphorylation of STAT1 at position 701 (Tyr701).